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US9442116B2 - Method of predicting chemotherapeutic responsiveness of cancer - Google Patents

Method of predicting chemotherapeutic responsiveness of cancer Download PDF

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Publication number
US9442116B2
US9442116B2 US12/765,995 US76599510A US9442116B2 US 9442116 B2 US9442116 B2 US 9442116B2 US 76599510 A US76599510 A US 76599510A US 9442116 B2 US9442116 B2 US 9442116B2
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Prior art keywords
formalin
fixed paraffin
clinical sample
rna
embedded clinical
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US12/765,995
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US20100292087A1 (en
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Johnathan M. Lancaster
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University of South Florida St Petersburg
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University of South Florida St Petersburg
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Assigned to UNIVERSITY OF SOUTH FLORIDA reassignment UNIVERSITY OF SOUTH FLORIDA ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LANCASTER, JOHNATHAN M.
Publication of US20100292087A1 publication Critical patent/US20100292087A1/en
Assigned to US ARMY, SECRETARY OF THE ARMY reassignment US ARMY, SECRETARY OF THE ARMY CONFIRMATORY LICENSE (SEE DOCUMENT FOR DETAILS). Assignors: H. LEE MOFFITT CANCER CTR & RESEARCH INS
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407Specifically defined cancers
    • G01N33/57449Specifically defined cancers of ovaries
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/502Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
    • G01N33/5023Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects on expression patterns
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/44Multiple drug resistance

Definitions

  • This invention relates to cancer diagnosis methods. Specifically, the invention is a method of determining the response of a cancer to chemotherapy using gene expressions of formalin-fixed paraffin embedded tissue samples.
  • tissue banks are invaluable resources of tissues for translational studies of cancer and various other diseases. Accessibility of macromolecules in the samples is a critical issue, as FFPE samples are traditionally limited to IHC.
  • a predictor for ovarian cancer response to platinum-based therapy is needed for use with stable patient samples, such as formalin fixed paraffin embedded samples.
  • the gene expression may be obtained from any number of means known in the art, including without limitation, Polymerase Chain Reaction, ChIp, gene array, microarrays or quantitative-Polymerase Chain Reaction (Q-PCR), and reverse transcriptase Polymerase Chain Reaction (rt-PCR).
  • the present method utilizes a novel genetic screen to identify genes that contribute to chemotherapeutic responsiveness, using formalin fixed paraffin embedded clinical samples.
  • a microarray screen showed formalin fixed paraffin embedded samples can identify genes related to chemotherapeutic response with 86% efficiency.
  • At least one threshold value is defined for classifying the gene expression levels.
  • the extracted biological material is selected from the group consisting of DNA, RNA, protein, derivatives thereof, and fragments thereof.
  • derivatives refer to processed variants of DNA, RNA, or proteins, which includes, without limiting the scope of the invention, transcripts.
  • the disclosed method uses RNA to determine gene expression. Gene expression levels are determined from the biological material in the clinical sample and compared to the gene expression of the clinical sample with a gene expression of known clinical outcome, indicative of tumor outcome.
  • the method is useful for predicting tumor responsiveness to chemotherapeutic treatment selected from the group consisting of alkylating agent, antimetabolite, plant alkaloid, and antitumor antibiotic. In further embodiments, the method is useful for predicting tumor responsiveness to cisplatin.
  • the disclosed methods utilize Polymerase Chain Reaction, ChIp, gene array, microarrays, reverse transcriptase Polymerase Chain Reaction, and quantitative-Polymerase Chain Reaction to determine gene expression in some embodiments.
  • the methods further generated a probeset list and tested the plurality of gene expressions in the clinical sample for gene expression using the probeset list.
  • the probeset list was generated by providing a first probeset and testing the first probeset against gene expression data for a tumor cell with known chemotherapeutic outcome, wherein the gene expression data is compared to the known chemotherapeutic outcome.
  • the chemotherapeutic treatment is selected from the group consisting of alkylating agent, antimetabolite, plant alkaloid, and antitumor antibiotic, and in more specific embodiments, the chemotherapeutic is cisplatin.
  • “Patient” is used to describe an animal, preferably a human, to whom treatment is administered, including prophylactic treatment with the compositions of the present invention.
  • a tumor prognosis predictor based on gene expression signatures of cancer cells.
  • Gene expression data is used to identify a patient's tumor response to chemotherapeutic intervention.
  • the invention uses cumulative expression information from a series of genes involved in the regulation of the cell cycle and the mitotic process. This information is then used to categorize tumor samples based on the chemotherapeutic responsiveness using a mathematical model and gene expression data derived from microarrays or quantitative-Polymerase Chain Reaction (Q-PCR) data.
  • Q-PCR quantitative-Polymerase Chain Reaction
  • Training set GeneChip results were subjected to ANOVA and Binary regression analysis to develop and test gene expression profiles associated with ovarian cancer platinum-responsiveness.
  • the 115 probe set predictor shown in FIG. 1 , was used to test the patient samples.
  • the Predictor correctly identified 27/33 (82%) platinum complete responders (CR) and 10/11 (91%) incomplete responders (IR) for an overall accuracy of 37/44 (84%) in leave-one-out cross validation.
  • the 115 probe set predictor correctly identified 26/32 (81%) CR and 9/11 (82%) IR samples, with an overall accuracy of 35/43 (81%).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Hospice & Palliative Care (AREA)
  • Oncology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
US12/765,995 2007-10-23 2010-04-23 Method of predicting chemotherapeutic responsiveness of cancer Expired - Fee Related US9442116B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/765,995 US9442116B2 (en) 2007-10-23 2010-04-23 Method of predicting chemotherapeutic responsiveness of cancer

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US98196307P 2007-10-23 2007-10-23
PCT/US2008/080939 WO2009055559A1 (fr) 2007-10-23 2008-10-23 Procédé de prévision de réponse chimiothérapeutique d'un cancer
US12/765,995 US9442116B2 (en) 2007-10-23 2010-04-23 Method of predicting chemotherapeutic responsiveness of cancer

Related Parent Applications (1)

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PCT/US2008/080939 Continuation WO2009055559A1 (fr) 2007-10-23 2008-10-23 Procédé de prévision de réponse chimiothérapeutique d'un cancer

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US20100292087A1 US20100292087A1 (en) 2010-11-18
US9442116B2 true US9442116B2 (en) 2016-09-13

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Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015013547A1 (fr) * 2013-07-24 2015-01-29 Cedars-Sinai Medical Center Utilisation de galnac-t13 comme marqueur dans le diagnostic du cancer du sein ou du côlon

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030225528A1 (en) * 2002-03-13 2003-12-04 Baker Joffre B. Gene expression profiling in biopsied tumor tissues
US20060154250A1 (en) 2002-12-17 2006-07-13 Morris David W Novel compositions and methods in cancer
US20070172844A1 (en) 2005-09-28 2007-07-26 University Of South Florida Individualized cancer treatments

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030225528A1 (en) * 2002-03-13 2003-12-04 Baker Joffre B. Gene expression profiling in biopsied tumor tissues
US20060154250A1 (en) 2002-12-17 2006-07-13 Morris David W Novel compositions and methods in cancer
US20070172844A1 (en) 2005-09-28 2007-07-26 University Of South Florida Individualized cancer treatments

Non-Patent Citations (22)

* Cited by examiner, † Cited by third party
Title
Affimetrix GeneChip Human Genome U133 2.0 Arrays FAQ; http://www.affymetrix.com/support/help/faqs/hgu133-2/faq-7.jsp; accessed Jul. 13, 2012. *
Affymetrix, Inc., Apr. 2003; Data Sheet: GeneChip Human Genome Arrays; p. 2 for "human datasheet".
Affymetrix, Inc., Aug. 20, 2008; HG-U133-Plus-2 Probe Sequences, FATSA for the text file.
Aviel-Ronen et al. 2006. "Large Fragment Bst DNA Polymerase for Whole Genome Amplification of DNA From Formalin-Fixed Paraffin-Embedded Tissues." BMC Genomics. vol. 7. No. 312. pp. 1-10.
Collet et al. 1994. "The Identification of Nuclear and Mitochondrial Genes by Sequencing Randomly Chosen Clones from a Marsupial Mammary Gland cDNA Library." Biochem Genet. vol. 32. Nos. 5/6. pp. 181-190.
Cook et al. 2000. "Binary Response and Logistic Regression Analysis." Part of the Iowa State University NSF/ILI Project Beyond Traditional Statistical Methods. http://www.faculty.sbc.edu/bkirk/Biostatistics/course%20documents%20for%202006/Logistic%20Regression%20Analysis.doc.
Crockett et al. 2005. "Identification of Proteins From Formalin-Fixed Paraffin-Embedded Cells by LC-MS/MS." Laboratory Investigation. vol. 85. pp. 1405-1415.
Dressman et al. 2007. "An Integrated Genomic-Based Approach to Individualized Treatment of Patients with Advanced-Stage Ovarian Cancer" Journal of Clinical Oncology. vol. 25. No. 5. pp. 517-525.
Dressman et al.; Retraction of the article "An Integrated Genomic-Based Approach to Individualized Treatment of Patients With Advanced-Stage Ovarian Cancer"; J Clin Oncol 25:517-525, 2007; published Jan. 27, 2012. *
Dubeau et al. 1986. "Southern Blot Analysis of DNA Extracted From Formalin-Fixed Pathology Specimens." Cancer Research. vol. 46. pp. 2964-2969.
Fox et al. 1985. "Formaldehyde Fixation." J. Histochem. Cytochem. vol. 33. No. 8. pp. 845-853.
Genome Reference Consortium Feb. 2009; GeneChip Human Genome U133 Plus 2.0 Array for "gene sequence source" doc.
Hood et al. 2006. "Unravelling the Proteome of Formalin-Fixed Paraffin-Embedded Tissue." Briefings in Functional Genomics and Proteomics. vol. 5. No. 2. pp. 169-175.
International Search Report for PCT/US20081/080939 dated Jan. 5, 2009.
Kunkel et al. 1981. "Contact-Site Cross-Linking Agents." Mol. Cell. Biochem. vol. 34. pp. 3-13.
Nugen Technologies, Inc. "WT-Ovation FFPE RNA Amplification System V2." www.nugenine.com. User Guide. Catalog # 3400-12, 3400-60. Version 05.09.08. pp. i-18.
Nugen Technologies, Inc. 2007. "RNA Sample Quality Assessment Test for the WT-Ovation FFPE System." www.nugenine.com.
Roche. 2008. "High Pure RNA Paraffin Kit." www.roche-applied-science.com. Cat. No. 03 270 289 001. pp. 1-24.
Shedden et al. 2008. "Gene Expression-Based Survival Prediction in Lung Adenocarcinoma: a Multi-Site, Blinded Validation Study." Nat. Med. vol. 14. No. 8. pp. 822-827.
Shi et al. 1991. "Antigen Retrieval in Formalin-Fixed, Paraffin-Embedded Tissues: an Enhancement Method for Immunohistochemical Staining Based on Microwave Oven Heating of Tissue Sections." J. Histochem Cytochem. vol. 39. No. 6. pp. 741-748.
Shi et al. 2002. DNA Extraction from Archival Formalin-Fixed, Paraffin-Embedded Tissue Sections Based on the Antigen Retrieval Principle: Heating Under the Influence of pH. The Journal of Histochemistry & Cytochemistry. vol. 50. No. 8. pp. 1005-1011.
West et al.; Predicting the clinical status of human breast cancer by using gene expression profiles; PNAS; vol. 98, No. 20, 11462-11467; Sep. 25, 2001. *

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WO2009055559A1 (fr) 2009-04-30

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